ZIF-8 nanoparticles induce neurobehavioral disorders through the regulation of ROS-mediated oxidative stress in zebrafish embryos

Hongmei Hu; Meile Su; Huixia Ba; Guilan Chen; Jiaqi Luo; Fasheng Liu; Xinjun Liao; Zigang Cao; Junquan Zeng; Huiqiang Lu; Guanghua Xiong; Jianjun Chen

doi:10.1016/j.chemosphere.2022.135453

ZIF-8 nanoparticles induce neurobehavioral disorders through the regulation of ROS-mediated oxidative stress in zebrafish embryos

Chemosphere. 2022 Oct:305:135453. doi: 10.1016/j.chemosphere.2022.135453. Epub 2022 Jun 22.

Authors

Hongmei Hu¹, Meile Su², Huixia Ba², Guilan Chen², Jiaqi Luo², Fasheng Liu², Xinjun Liao², Zigang Cao², Junquan Zeng², Huiqiang Lu², Guanghua Xiong³, Jianjun Chen⁴

Affiliations

¹ Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; Center of Clinical Medicine Research, College of Life Sciences, Jinggangshan University, Ji'an, 343009, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, 343009, Jiangxi, China.
² Center of Clinical Medicine Research, College of Life Sciences, Jinggangshan University, Ji'an, 343009, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, 343009, Jiangxi, China.
³ Center of Clinical Medicine Research, College of Life Sciences, Jinggangshan University, Ji'an, 343009, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, 343009, Jiangxi, China. Electronic address: xionggh@jgsu.edu.cn.
⁴ Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China. Electronic address: chenjianjun@tongji.edu.cn.

PMID: 35752317
DOI: 10.1016/j.chemosphere.2022.135453

Abstract

Zeolite imidazolate framework-8 (ZIF-8) is a nanomaterial of metal-organic frameworks (MOFs), which have various applications in drug delivery and water pollution remediation. However, little is known about its developmental neurotoxicity in aquatic organisms, especially on the low-level exposure. In the present study, we investigated the toxic effects of ZIF-8 NPs on the neuron development, behavioral traits, oxidative stress and gene expression in zebrafish embryos. Firstly, our results showed that ZIF-8 induced significantly embryonic malformations and abnormal development of nervous system in zebrafish embryos with a concentration-dependent manner. Meanwhile, the locomotor behavior was obviously inhibited while the anxiety behavior was greatly increased after ZIF-8 exposure. Secondly, the levels of ROS and antioxidant enzyme activities (CAT, SOD and MDA) together with AChE and ATPase were substantially increased in the ZIF-8 exposed groups. At the molecular level, ZIF-8 NPs could down-regulate the expression profiles of neural development-related genes (gap43, synapsin 2a and neurogenin 1) and PD-like related genes (dj-1, dynactin and parkin), but up-regulate the expression levels of neuro-inflammatory genes (nox-1, glip1a and glip1b) in larval zebrafish. In addition, we further explored the molecular mechanism of neurotoxicity induced by ZIF-8 with pharmacological experiments. The results showed that specific inhibition of ROS-mediated oxidative stress by the astaxanthin could reverse the expression patterns of ATPase, AChE and neurodevelopmental genes. Moreover, astaxanthin can partially rescue the ZIF-8-modulated locomotor behavior. Taken together, our results demonstrated that ZIF-8 had the potential to cause neurotoxicity in zebrafish embryos. These informations presented in this study will help to elucidate the molecular mechanisms of ZIF-8 nanoparticles exposure in zebrafish, which providing a scientific evaluation of its safety to aquatic ecosystems.

Keywords: Locomotor behavior; Neuroinflammation; Neurotoxicity; Oxidative stress; ZIF-8; Zebrafish.

MeSH terms

Adenosine Triphosphatases / metabolism
Animals
Antioxidants / metabolism
Ecosystem
Embryo, Nonmammalian
Nanoparticles*
Oxidative Stress
Reactive Oxygen Species / metabolism
Water Pollutants, Chemical* / metabolism
Zebrafish / metabolism
Zeolites* / toxicity

Substances

Antioxidants
Reactive Oxygen Species
Water Pollutants, Chemical
Zeolites
Adenosine Triphosphatases